A prospective randomized trial of continuous infusion 5-fluorouracil (5-FU) versus 5-FU plus cisplatin in patients with advanced colorectal cancer. A trial of the Spanish Cooperative Group for Digestive Tract Tumor Therapy (T.T.D.).

One hundred sixty consecutive patients with histologically confirmed colorectal cancer (advanced disease) without prior chemotherapy were entered in a randomized trial comparing 5-fluorouracil (5-FU) 1,000 mg/m2 intravenously per day for 5 consecutive days in continuous infusion versus cisplatin (CP) 100 mg/m2 on day 1 plus 5-FU as described on days 2 to 6. In both arms, treatment was recycled every 4 weeks. Both groups were well balanced for age, sex, colon or rectal origin, median time between diagnosis to advanced disease, performance status at entry, and visceral involvement. The overall response rate in the combination and in the single arm were 18 and 23%, respectively. There were no differences in time to progression (a median of 17.8 and 14.9 weeks for CP-5-FU and 5-FU, respectively) and in overall survival (a median of 71.2 and 59.6 weeks, respectively). The incidence of grade 3-4 emesis was significantly higher in the CP-containing chemotherapy (p = .00001). Our study has failed to demonstrate any clinical benefit from adding cisplatin to 5-FU in patients with cancer of the colon and rectum.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients.

BACKGROUND: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. METHODS: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. RESULTS: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (-2.6 +/- 0.9%, -5.1 +/- 1.8%, -12.5 +/- 4.2%, respectively), ALEN (-2.8 +/- 0.8%, -5.3 +/- 1.6%, -12.0 +/- 3.9%) and ALEN + TRN groups (-2.7 +/- 1.0%, -5.6 +/- 2.1%, -11.2 +/- 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. CONCLUSIONS: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.     

Diagnosis of pulmonary Kaposi's sarcoma with fiberoptic bronchoscopy and endobronchial biopsy. A report of five cases

Fiberoptic bronchoscopy is a major tool in the diagnostic evaluation of pulmonary disease in patients with the Acquired Immune Deficiency Syndrome. Multiple opportunistic infections and Kaposi's sarcoma affect the lung in this disorder. In contrast to opportunistic infections, Kaposi's sarcoma is rarely reported to be diagnosed by means of bronchoscopy. This report describes five of seven patients in whom endobronchial lesions consistent with submucosal involvement by the tumor were seen, and Kaposi's sarcoma was diagnosed without complication. Kaposi's sarcoma must be considered in the differential diagnosis of pulmonary disease in patients with a proven extrapulmonary tumor focus, and fiberoptic bronchoscopy is the initial diagnostic procedure of choice. Endobronchial Kaposi's sarcoma may be a marker for parenchymal involvement by the tumor. Diagnosis of endobronchial Kaposi's sarcoma can be an important factor in decisions regarding therapy.     

Myelolipoma: A New Adrenal Finding in Carney's Complex?

Pigmented nodular cortical hyperplasia, a rare cause of Cushing’s syndrome, is characterized by resistance to inhibition with dexamethasone and normal sized adrenal glands with multiple, small pigmented nodules. The disorder may be a component of a syndrome inherited as an autosomal dominant pattern that includes intra- and extracardiac myxomas, lentiginous lesions, blue nevi, other functional endocrine tumors, and peripheral nerve tumors (Carney’s complex). We report a patient in whom bilateral myelolipomas were found, in addition to the usual features of this complex. A 29-yr-old man was admitted to the hospital for Cushing’s syndrome of probably more than 15 yr duration. Physical examination showed diffuse facial hyperchromatic macules, 0.2–0.5 cm, predominantly around the lips and on the palmar surfaces of the fingers. Results with dexamethasone suppression nocturnal testing (1 and 8 mg) were compatible with an adrenal adenoma. The computed tomography (CT) of the sella turcica was normal. Adrenal CT showed a tumor in the left gland with a double component: one solid and another suggestive of fat, consistent with an angiomyelolipoma. Following 5 wk treatment with ketoconazole, 800 mg per day po, serum cortisol decreased to 5.9 μg/dL, morning and evening, respectively. Bilateral adrenalectomy was performed. Pathologic examination revealed pigmented nodular cortical hypersplasia and a dominant myelolipoma in the left adrenal. A microscopic myelolipoma was identified in the right adrenal. An echocardiogram showed a mass on the posterior wall of the left ventricle which was a myxoma. Study of the patient's family disclosed two sisters with facial lentigines. Echocardiograms were performed on all available first degree relatives: all were normal. Nocturnal inhibition with dexamethasone revealed that one of the patient’s sisters with lentigines also had hypercortisolism. Myelolipoma has been reported in association to Cushing syndrome in humans and experimentally after pituitary extracts in animals. The relationship between this finding and the Carney’s complex remain elusive.     

Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…